ScienceDaily (Dec. 27, 2009) — A new study finds that the herb milk thistle may help treat liver inflammation in cancer patients who receive chemotherapy. Published early online in Cancer, a peer-reviewed journal of the American Cancer Society, the study indicates that the herb could allow patients to take potent doses of chemotherapy without damaging their liver.

Chemotherapy drugs frequently cause inflammation in the liver, and when they do, doctors must often lower patients’ doses or stop administering the therapies altogether. Clinical studies have investigated using milk thistle to treat liver damage from cirrhosis (from alcohol) or toxins (such as mushroom poisoning). Despite limited study data, the herb is often used for the treatment of chemotherapy associated liver problems. To test whether milk thistle could help treat chemotherapy associated liver problems, Kara Kelly, MD, of the New York-Presbyterian Hospital/Columbia University Medical Center’s Herbert Irving Comprehensive Cancer Center in New York City and colleagues conducted a randomized, controlled, double blind study in children with acute lymphoblastic leukemia (ALL), who commonly experience this side effect.

Fifty children with ALL were enrolled in the study and were randomized to receive milk thistle or placebo for 28 days. At the start of the study, all of the children had evidence of liver inflammation as measured by elevations in blood levels of the liver enzymes, aspartate amino transferase (AST) and amino alanine transferase (ALT). When the investigators performed liver function tests on the children at day 56 (28 days after receiving the herb or placebo), children receiving milk thistle had improvements in their liver enzymes compared with children receiving a placebo. Specifically, the group that took milk thistle had significantly lower levels of AST and a trend towards significantly lower levels of ALT. Taking milk thistle also seemed to help keep fewer patients from having to lower the dose of their medications: chemotherapy doses were reduced in 61 percent of the group receiving milk thistle, compared with 72 percent of the placebo group. In addition, milk thistle appeared to be safe for consumption.

The researchers also studied the effects of combining milk thistle with chemotherapy on leukemia cells grown in the laboratory. They found that milk thistle does not interfere with the cancer-fighting properties of chemotherapy.

“Milk thistle needs to be studied further, to see how effective it is for a longer course of treatment, and whether it works well in reducing liver inflammation in other types of cancers and with other types of chemotherapy,” said Dr. Kelly. “However, our results are promising as there are no substitute medications for treating liver toxicity.”

Ladas et al. A randomized, controlled, double-blind, pilot study of milk thistle for the treatment of hepatotoxicity in childhood acute lymphoblastic leukemia (ALL). Cancer, 2009; DOI: 10.1002/cncr.24723

ScienceDaily (Dec. 8, 2009) — A new study finds that compounds derived from the spices turmeric and pepper could help prevent breast cancer by limiting the growth of stem cells, the small number of cells that fuel a tumor’s growth.

Researchers at the University of Michigan Comprehensive Cancer Center have found that when the dietary compounds curcumin, which is derived from the Indian spice turmeric, and piperine, derived from black peppers, were applied to breast cells in culture, they decreased the number of stem cells while having no effect on normal differentiated cells.

“If we can limit the number of stem cells, we can limit the number of cells with potential to form tumors,” says lead author Madhuri Kakarala, M.D., Ph.D., R.D., clinical lecturer in internal medicine at the U-M Medical School and a research investigator at the VA Ann Arbor Healthcare System.

Cancer stem cells are the small number of cells within a tumor that fuel the tumor’s growth. Current chemotherapies do not work against these cells, which is why cancer recurs and spreads. Researchers believe that eliminating the cancer stem cells is key to controlling cancer. In addition, decreasing the number of normal stem cells — unspecialized cells that can give rise to any type of cell in that organ — can decrease the risk of cancer.

In this study, a solution of curcumin and piperine was applied to the cell cultures at the equivalent of about 20 times the potency of what could be consumed through diet. The compounds are available at this potency in a capsule form that could be taken by mouth.

The researchers applied a series of tests to the cells, looking at markers for breast stem cells and the effects of curcumin and piperine, both alone and combined, on the stem cell levels. They found that piperine enhanced the effects of curcumin, and that the compounds interrupted the self-renewal process that is the hallmark of cancer-initiating stem cells. At the same time, the compounds had no affect on cell differentiation, which is the normal process of cell development.

“This shows that these compounds are not toxic to normal breast tissue,” Kakarala says. “Women at high risk of breast cancer right now can choose to take the drugs tamoxifen or raloxifene for prevention, but most women won’t take these drugs because there is too much toxicity. The concept that dietary compounds can help is attractive, and curcumin and piperine appear to have very low toxicity.”

Curcumin and piperine have been explored by other researchers as a potential cancer treatment. But this paper, published online in the journal Breast Cancer Research and Treatment, is the first to suggest these dietary compounds could prevent cancer by targeting stem cells.

In addition, tamoxifen or raloxifene are designed to affect estrogen, which is a factor in most, but not all breast cancers. In fact, the aggressive tumors that tend to occur more often in women with a family history or genetic susceptibility are typically not affected by estrogen. Because curcumin and piperine limit the self renewal of stem cells, they would impact cancers that are not estrogen sensitive as well as those that are.

Researchers are planning an initial Phase I clinical trial to determine what dose of curcumin or piperine can be tolerated in people. The trial is not expected to begin accruing participants until spring.

Breast cancer statistics: 194,280 Americans will be diagnosed with breast cancer this year and 40,610 will die from the disease, according to the American Cancer Society

Additional authors include Dean Brenner, Hasan Korkaya, Connie Cheng, Karim Tazi, Christophe Ginestier, Suling Liu, Gabriel Dontu and Max Wicha, all from U-M

Funding was provided by the National Institutes of Health; curcumin and piperine were donated by Sabinsa Co.

Journal Reference:

1. Madhuri Kakarala, Dean E. Brenner, Hasan Korkaya, Connie Cheng, Karim Tazi, Christophe Ginestier, Suling Liu, Gabriela Dontu and Max S. Wicha. Targeting breast stem cells with the cancer preventive compounds curcumin and piperine. Breast Cancer Research and Treatment, 2009; DOI: 10.1007/s10549-009-0612-x

ScienceDaily (Dec. 9, 2009) — A new study has found that the amount of vitamin D in patients being treated for diffuse large B-cell lymphoma was strongly associated with cancer progression and overall survival. The results will be presented at the annual meeting of the American Society of Hematology in New Orleans.

“These are some of the strongest findings yet between vitamin D and cancer outcome,” says the study’s lead investigator, Matthew Drake, M.D., Ph.D., an endocrinologist at Mayo Clinic in Rochester. “While these findings are very provocative, they are preliminary and need to be validated in other studies. However, they raise the issue of whether vitamin D supplementation might aid in treatment for this malignancy, and thus should stimulate much more research.”

The researchers’ study of 374 newly diagnosed diffuse large B-cell lymphoma patients found that 50 percent had deficient vitamin D levels based on the commonly used clinical value of total serum 25(OH)D less than 25 ng/mL. Patients with deficient vitamin D levels had a 1.5-fold greater risk of disease progression and a twofold greater risk of dying, compared to patients with optimal vitamin D levels after accounting for other patient factors associated with worse outcomes.

The study was conducted by a team of researchers from Mayo Clinic and the University of Iowa. These researchers participate in the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE), which is funded by the National Cancer Institute. The 374 patients were enrolled in an epidemiologic study designed to identify predictors of outcomes in lymphoma. Since this was not a clinical trial, patient management and treatments were not assigned, but rather followed standard of care for clinical practice.

The findings support the growing association between vitamin D and cancer risk and outcomes, and suggest that vitamin D supplements might help even those patients already diagnosed with some forms of cancer, says Dr. Drake. “The exact roles that vitamin D might play in the initiation or progression of cancer is unknown, but we do know that the vitamin plays a role in regulation of cell growth and death, among other processes important in limiting cancer,” he says.

The findings also reinforce research in other fields that suggest vitamin D is important to general health, Dr. Drake says. “It is fairly easy to maintain vitamin D levels through inexpensive daily supplements or 15 minutes in the sun three times a week in the summer, so that levels can be stored inside body fat,” he says. Many physicians recommend 800-1,200 International Units (IU) daily, he adds.

Vitamin D is a steroid hormone obtained from sunlight and converted by the skin into its active form. It also can come from food (naturally or fortified as in milk) or from supplements. It is known best for its role of increasing the flow of calcium into the blood. Because of that role, vitamin D deficiency has long been known to be a major risk factor for bone loss and bone fractures, particularly in elderly people whose skin is less efficient at converting sunlight into vitamin D. But recent research has found that many people suffer from the deficiency, and investigators are actively looking at whether low vitamin D promotes poorer health in general.

Cancer researchers have discovered that vitamin D regulates a number of genes in various cancers, including prostate, colon and breast cancers. Recent studies have suggested that vitamin D deficiency may play a role in causing certain cancers as well as impacting the outcome once someone is diagnosed with cancer.

Researchers looked at vitamin D levels in lymphoma patients because of the observation, culled from U.S. mortality maps issued by the National Cancer Institute, that both incidence and mortality rates of this cancer increase the farther north a person lives in the United States, where sunlight is limited in the winter. Also, several recent reports have concluded that vitamin D deficiency is associated with poor outcomes in other cancers, including breast, colon and head and neck cancer. This is the first study to look at lymphoma outcome.

The study was funded by the National Cancer Institute and the Mayo Hematologic Malignancies Lymphoma Fund.

Background Chinese medicine often targets more than one system and as such comprises several compounds, often in non-purified form, with treatments therefore consisting of whole extracts of herbs rather than isolated compounds. The additive and synergistic effects of the phytochemicals in OMN54, a novel mixture of extracts from three commonly used Chinese medicine components; Ganoderma lucidum, Salvia miltiorrhiza and Scutellaria barbata, were previously demonstrated to have potent anti-cancer activity. This study aims to test whether this heterogeneous, multifunctional and multitargeted agent has an acceptable toxicity profile. Methods We conducted preliminary and formal preclinical tolerability determination of OMN54 in Sprague-Dawley rats. In the preliminary study rats were given OMN54 by oral feeding daily for 14 days at doses of 1000mg/kg, 1750mg/kg, 2500mg/kg or 3000mg/kg per day. A subsequent daily dosing (x 28, 60, 120 or 180) formal toxicology study was conducted in male and female Sprague-Dawley rats at a dose of single dose of 2000mg/kg/day. Results Significant body weight loss was noted in one of the rats treated at 3000mg/kg/day, with decline beginning study day 11. This animal experienced mild GI toxicity in the form of diarrhoea. Gross observation indicated kidney damage (pale kidneys) in both this group and in one rat treated at 2500mg/kg/day. For the later studies, no body weight loss was noted over the course of the study. Blood counts and chemistry were not substantially altered following administration of OMN54, nor were there any findings on histological assessment of organs. Conclusion OMN54 was found to be well tolerated in rat models. OMN54 did not cause any microscopic, anatomic or pathologic changes in exposed animals at the concentrations and under the conditions employed in this study.

Chinese Medicine 2009, 4:22doi:10.1186/1749-8546-4-22

In the search for a more effective adjuvant therapy to treat multiple myeloma (MM), we investigated the effects of the traditional Chinese herbal medicines Huang-Lian-Jie-Du-Tang (HLJDT), Gui-Zhi-Fu-Ling-Wan (GZFLW), and Huang-Lian-Tang (HLT) on the proliferation and apoptosis of myeloma cells. HLJDT inhibited the proliferation of myeloma cell lines and the survival of primary myeloma cells, especially MPC-1^- immature myeloma cells, and induced apoptosis in myeloma cell lines via a mitochondria-mediated pathway by reducing mitochondrial membrane potential and activating caspase-9 and caspase-3. Further experiments confirmed that Scutellaria radix was responsible for the suppressive effect of HLJDT on myeloma cell proliferation, and the baicalein in Scutellaria radix showed strong growth inhibition and induction of apoptosis in comparison with baicalin or wogonin. Baicalein as well as baicalin suppressed the survival in vitro of MPC-1^- immature myeloma cells rather than MPC-1⁺ myeloma cells from myeloma patients. Baicalein inhibited the phosphorylation of IkB-, which was followed by decreased expression of the IL-6 and XIAP genes and activation of caspase-9 and caspase-3. Therefore, HLJDT and Scutellaria radix have an antiproliferative effect on myeloma cells, especially MPC-1^- immature myeloma cells, and baicalein may be responsible for the suppressive effect of Scutellaria radix by blocking IkB- degradation. (Blood. 2005;105:3312-3318)

Zi Ma, Ken-ichiro Otsuyama, Shangqin Liu, Saeid Abroun, Hideaki Ishikawa, Naohiro Tsuyama, Masanori Obata, Fu-Jun Li, Xu Zheng, Yasuko Maki, Koji Miyamoto, and Michio M. Kawano

From the Department of Bio-Signal Analysis, Applied Medical Engineering Science (AMES), Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan; and Department of Kampo Medicine, Molecular Science, and Applied Medicine, Yamaguchi University School of Medicine, Yamaguchi University, Yamaguchi, Japan.

Toxicology. 2009 Oct 7.

Burns JJ, Zhao L, Taylor EW, Spelman K.

Pinnacle Integrative Medicine, Phoenix, AZ, USA.

ScienceDaily (Nov. 5, 2009) — Green tea extract has shown promise as cancer prevention agent for oral cancer in patients with a pre-malignant condition known as oral leukoplakia, according to researchers at The University of Texas M. D. Anderson Cancer Center.

The study, published online in Cancer Prevention Research, is the first to examine green tea as a chemopreventative agent in this high-risk patient population. The researchers found that more than half of the oral leukoplakia patients who took the extract had a clinical response.

Long investigated in laboratory, epidemiological and clinical settings for several cancer types, green tea is rich in polyphenols, which have been known to inhibit carcinogenesis in preclinical models. Still, clinical results have been mixed.

“While still very early, and not definitive proof that green tea is an effective preventive agent, these results certainly encourage more study for patients at highest risk for oral cancer,” said Vassiliki Papadimitrakopoulou, M.D., professor in M. D. Anderson’s Department of Thoracic/Head and Neck Medical Oncology, and the study’s senior author. “The extract’s lack of toxicity is attractive — in prevention trials, it’s very important to remember that these are otherwise healthy individuals and we need to ensure that agents studied produce no harm.”

In the Phase II dose-finding study, 41 M. D. Anderson oral leukoplakia patients were randomized between August 2002 and March 2008 to receive either green tea extract or placebo. Participants took the extract, an oral agent, for three months at one of three doses — 500 per meter squared of body mass (mg/m2); 750 mg/m2 or 1,000 mg/m2 — three times daily. To best assess biomarkers, participants also underwent a baseline and 12-week biopsy, an important component in the design of the study, the researchers say.

“Collecting oral tissue biopsies was essential in that it allowed us to learn that not only did the green tea extract appear to have benefit for some patients, but we pointed to anti-angiogenic effects as a potential mechanism of action,” said Anne Tsao, M.D., assistant professor in the Department of Thoracic/Head and Neck Medical Oncology, and the study’s first author. “While preliminary because our patient population was so small, this gives us direction for further study.”

Of those taking green tea at the two highest doses, 58.8 percent had a clinical response, compared with 36.4 percent in the lowest extract dose and 18.2 percent in the placebo arm. At an extended follow-up with a mean of 27.5 months, 15 participants had developed oral cancer, with a median time to disease development of 46.4 months.

Although not statistically significant, the green tea extract also improved histology and trended towards an improvement in a number of biomarkers that may play a vital role in predicting cancer development.

Another important finding, say the researchers, was that that the extract was well tolerated. Side effects, including insomnia and nervousness, were mostly seen in the high-dose group but produced no significant toxicity.

“While these are encouraging findings, much more research must be done before we can conclude that green tea may prevent oral or any other type of cancer. It’s also important to remind people that this trial enrolled very few participants who, at the highest dose levels took the equivalent of eight cups of green tea three times a day,” said Papadimitrakopoulo. “We need to further understand if green tea offers longer-term prevention effects for patients.”

Papadimitrakopoulo and Tsao think that future studies with green tea in this high-risk population should focus on participants being exposed to the supplement for a longer time period. The researchers also stressed that the green tea extract studied in this trial was never sold over-the-counter and/or the Internet, both of which are not highly regulated. Rather, the compound was exclusively developed as a pharmaceutical.

According to the American Cancer Society, more than 35,720 are expected to be diagnosed with oral and/or pharynx cancer and the five year survival rate is less than 50 percent.

The study was funded by Ito En, the company that produced the green tea extract.

In addition to Papadimitrakopoulou and Tsao, other M. D. Anderson authors on the study include: Waun Ki Hong, M.D., professor and chair of the Division of Cancer Medicine; Jack Martin, D.D.S., professor in the Department of Dental Oncology; Li Mao, M.D., adjunct professor and Xi Ming Tang, M.D., Ph.D. research scientist, both of the Department of Thoracic/Head and Neck Medical Oncology; Adel El-Naggar, M.D., Ph.D., professor in the Department of Pathology; Iganacio Wistuba, M.D., professor in the Department of Pathology-Research; Kirk Culotta, Phar M.D., Department of Pharmacy Pharmacology Research; Ann Gillenwater, M.D., professor in the Department of Head and Neck Surgery; J. Jack Lee, Ph.D., professor and Diane Liu, both of the Department of Biostatistics. Other authors include Yuko Sagesaka of Ito En, Ltd.

ScienceDaily (Oct. 26, 2009) — Antioxidant extracts of the leaves of the Gingko biloba tree may protect cells from radiation damage, according to a study published in the International Journal of Low Radiation. The discovery may one day be used to help reduce side effects in cancer patients undergoing radiotherapy.

Chang-Mo Kang of the Korea Institute of Radiological and Medical Sciences in Taegu and colleagues are interested in the protective effects of well-known herbal remedies of which Gingko biloba is one. G. biloba is a unique tree species with no close living relatives and extracts of its leaves contain antioxidant compounds including glycosides and terpenoids known as ginkgolides and bilobalides.

These compounds are thought to protect cells from damage by free radicals and other reactive oxidizing species found in the body. These are generated continuously by the body’s normal metabolism, and in excess in some diseases or after exposure to pollution or radiation. They damage proteins, DNA and other biomolecules and left unchecked can kill cells.

As such, extracts of certain plants that contain antioxidants, including G. biloba, have attracted interest for their pharmacological activity. G. biloba is currently sold as a herbal supplement and there are numerous claims for health benefits, including the possibility of preventing the onset of dementia or Alzheimer’s disease.

Kang and colleagues have now collected human white blood cells, lymphocytes, from healthy donors aged 18 to 50 years. They treated half of these cells with commercially available G. biloba extract in the laboratory and doused the other half with salt solution as an experimental control. They then compared the effects of gamma radiation from radioactive cesium on the white blood cells compared to the untreated control samples.

The team uses a light microscope to look for lymphocytes undergoing programmed cell death, or apoptosis, as a result of radiation exposure. They found that there was a significant increase in apoptosis in the untreated cells compared with those treated with G. biloba extract. Almost a third of the untreated cells underwent apoptosis compared with approximately one in twenty of the treated cells. Parallel studies with laboratory mice also demonstrated a similar protective effect against radiation poisoning.

The results suggest that the extracts can neutralize the free-radicals and oxidizing agents produced in the cells by the radiation and so prevent them from undergoing apoptosis.

1. Shin et al. Protective effect of Gingko biloba against radiation-induced cellular damage in human peripheral lymphocytes and murine spleen cells. International Journal of Low Radiation, 2009; 6 (3): 209 DOI: 10.1504/IJLR.2009.028889

ScienceDaily (Sep. 29, 2008) — Gecko is a Chinese traditional medicine. It has definite effect on malignant tumor, especially on digestive system tumor. The incidence and mortality of tumor keep ascending all over the world. However, there was no study on the pharmacological studies of Gecko and its mechanisms of anti-tumor action remained unclear.

Now a research group in China has found that Gecko powder can inhibit EC9706 and EC1 growth and proliferation.

Gecko can also decrease vascular endothelin growth factor and basic fibroblast growth factor expression in tumor tissue and induce tumor cell apoptosis.

As is known, the effect on anti-tumor of traditional Chinese medicine (TCM) is related to more pathways and more targets. Most studies on action mechanisms of TCM in anti-tumor showed that TCM could inhibit tumors though supporting the healthy energy and strengthening the body resistance.

The research team, led by Prof. Wang from Henan University of China, showed that Gecko could not only reinforce immunity of organism but also induction of tumor cell apoptosis and the down-regulation of protein expression of VEGF and bFGF.

Chemotherapy, one of the major methods to treat cancer in Western medicine at present, has a poor selectivity and strong toxic and side effects, thus influencing its anticancer effect. In the past 40 years, Chinese experts have gained remarkable achievements in cancer treatment by integrating TCM with chemotherapy. This article gives us pharmacological studies of Gecko about antitumor and thus may provide foundation for its effective constituent.

1. Liu et al. Antitumor effect and mechanism of Gecko on human esophageal carcinoma cell lines in vitro and xenografted sarcoma 180 in Kunming mice. World Journal of Gastroenterology, 2008; 14 (25): 3990 DOI: 10.3748/wjg.14.3990

ScienceDaily (Dec. 31, 2008) — Medicinal plants have been used as traditional remedies for hundreds of years. Among them, S. barbata has been traditionally used in treatment of hepatitis, inflammation, osteomyelitis and gynecological diseases in China. Studies indicate that extracts from S. barbata have growth inhibitory effects on a number of human cancers. Reports are available on the treatment of lung, breast and digestive system cancer, hepatoma, and chorioepithelioma with S. barbata extracts.

However, the underlying mechanism of the antitumor activity of S. barbata extracts remains unclear.

A research team led by Dr. Zhi-Jun Dai from the Medical School of Xi’an Jiaotong University studied the growth inhibitory effects of S. barbata and determined its mechanism of antitumor activity in mouse liver cancer cell line H22.

They found that ESB could inhibit the proliferation of H22 cell in a time dependent manner. Among the various phases of cell cycle, the percentage of cells in S phase was significantly decreased, while the percentage of cells in G1 phase was increased. Flow cytometry assay also showed ESB had positive effect on apoptosis. Typical apoptotic morphology such as condensation and fragmentation of nuclei and blebbing membrane of the apoptotic cells could be observed through transmission electron microscope and fluorescence microscope. Further investigating the molecular mechanism behind ESB-induced apoptosis, cells treated with ESB underwent a rapid loss of mitochondrial transmembrane potential(delta psi m), release of mitochondrial cytochrome c into cytosol, induction of caspase-3 activity in a dose-dependent manner. This may offer new evidence for S. barbata in the treatment of hepatoma in clinical practice.

1. Dai ZJ, Wang XJ, Li ZF, Ji ZZ, Ren HT, Tang W, Liu XX, Kang HF, Guan HT, Song LQ. Scutellaria barbate extract induces apoptosis of hepatoma H22 cells via the mitochondrial pathway involving caspase-3. World J Gastroenterol, 14(48): 7321-7328